Description: (Applicant's Description) The ultimate goal of the Clinical Investigations Program is to develop more effective therapies for human cancer based on a better understanding of cancer biology and tumorigenesis. In pursuit of this goal, group members will integrate original laboratory studies of molecular mechanisms with innovative clinical trials. While tremendous progress has been made in understanding the molecular basis of oncogenesis, more effective therapies based on these molecular insights are needed. Ideally, development of new cancer therapies takes advantage of powerful molecular and cellular biology approaches to overcome the challenges facing cancer therapists. To that end, members in the Clinical Investigations Program embrace a multidisciplinary approach to treatment of specific cancers by integrating multiple modalities including surgery, chemotherapy, radiation therapy, and gene/immunotherapy. While the delivery and improvement of multidisciplinary care remains a major focus of the Clinical Investigations Program, translational research is its prime objective and is emphasized through working groups comprised of laboratory and clinical investigators. The goal of developing more effective, less toxic, cancer therapies will be pursued through these major specific aims: 1. To contribute to the discovery of biological molecules and biochemical pathways that influence tumor biology or represent potential new targets for treating patients with specific cancers. 2. To perform clinical studies that translate basic science observations into novel diagnostic and treatment approaches.